This proposal describes experiments investigating the interactions between Dirofilaria immitis, the nematode agent of dog heartworm, and various potential mosquito vector species. Previous studies have shown that various Florida mosquito species display a spectrum of responses to D. immitis infections, including death of the vector (Anopheles quadrimaculatus) successful development (Aedes taeniorhynchus) and death of the parasite (Aedes aegypti). We propose to make use of this spectrum of response, to analyze the mechanisms of parasite rejection in refractory species and the causes of differential mosquito death in susceptible species. Dirofilaria larvae spend the first three larval stages in the Malpighian tubules of the mosquitoes. Our preliminary studies demonstrate fundamental differences in cellular defense mechanisms of Malpighian tubules from susceptible and refractory mosquito species. We are examining the hypothesis that the ability of the Malpighian tubule cells to resist infection is related to their capacity to form a delimiting membrane and initiate a lysomal attack on the parasite. Parameters to be investigated in control and infected mosquitoes of all three species include: the presence or absence of a delimiting membrane around the parasite rejection; the ability of the Malpighian tubule cells to menalize parasites; the physiological role of the Malpighian tubules and the effects of massive parasitism on Malpighian tubule function. These studies are intended to provide a physiological basis at the cellular level for explaining the extreme variabilities observed in the vector capacities of mosquito species with regard to D. immitis and other nematodes.